Over the past five years, the literature on the psychiatric use of psychedelic and related treatments has expanded substantially. Several randomized controlled trials and pooled analyses have been conducted in mood disorders, treatment-resistant depression, and post-traumatic stress disorder. Trial methodology, however, remains a fundamental source of uncertainty, and despite the popularity of the field, the clinical evidence is still weak. Psilocybin produces consistent and often large improvements in major depressive disorder, yet in the most rigorous trials, the predefined primary endpoint does not always reach statistical significance. At the same time, a synthetic psilocybin (COMP360) met its primary endpoint in two phase 3 trials in 2025-2026, representing the most advanced regulatory evidence in the field to date. MDMA (3,4-methylenedioxymethamphetamine; "ecstasy")-assisted psychotherapy has the largest phase 3 dataset in post-traumatic stress disorder, but in 2024 the US Food and Drug Administration declined to approve the product on ethical grounds. Evidence for LSD (lysergic acid diethylamide) and ayahuasca in depressive and anxiety symptoms is considerably weaker and cannot yet be interpreted within an evidence-based medicine framework. The therapeutic use of psychedelics can no longer be regarded as merely a theoretical question or a subcultural movement: the clinical effect is consistent and, in several trials, markedly strong. Nevertheless, according to the international system grading the certainty of evidence, the level of certainty remains low or very low for several indications. The main reasons are practical unblinding, small sample sizes, trial heterogeneity, and a lack of long-term safety data. Despite encouraging phase 3 data, psilocybin and the classic psychedelics should be considered experimental treatments. For MDMA, the phase 3 results are promising but have not proven sufficient for regulatory approval. Orv Hetil. 2026; 167(37): 1461-1467.

Religion and spirituality may sustain healthcare workers through meaning, hope, relational connection, and vocational purpose, yet their restorative contribution may diminish under chronic and inadequately supported occupational demands. This conceptual article develops a sacred depletion process model for healthcare workers in the Philippines and proposes sacred burnout as a provisional outcome construct. Through integrative conceptual analysis, theory synthesis, and differential concept comparison, the article integrates religious coping theory with conservation of resources theory. It distinguishes the recursive sacred depletion process from the sacred burnout state and identifies reduced sacred restoration as the proposed mechanism connecting occupational resource loss with declining spiritual and vocational vitality. Sacred burnout is defined as spiritual and vocational exhaustion characterized by diminished restoration from sacred practices and meanings that remain valued within inadequately supported healthcare work. The model differentiates internalized sacred obligation from externally imposed sacred obligation and introduces institutional sacralization of sacrifice to explain how vocational, moral, religious, or heroic language may normalize excessive sacrifice or shift responsibility for unsafe working conditions to healthcare workers. It incorporates recursive relationships among boundary erosion, cumulative resource loss, sacred expectation conflict, and reduced sacred restoration while recognizing organizational, relational, psychological, and spiritual recovery pathways. Sacred burnout is distinguished provisionally from occupational burnout, compassion fatigue, moral injury, religious struggle, spiritual dryness, and depression. It is not a diagnosis, validated screening category, or measure of religious commitment. Its conceptual value depends on evidence of discriminant, incremental, and longitudinal validity. Sustainable responses require noncoercive spiritual care, differentiated psychological assessment, protected recovery, and institutional accountability.

Tyrosine kinase inhibitors (TKIs) improve survival for people with chronic myeloid leukemia (CML) but may cause adverse events (AEs) that impair quality of life (QoL). Adults with CML receiving first- or second-line TKI therapy in the United States (US) completed validated questionnaires to assess AEs (PRO-CTCAE), QoL (PROMIS Global Physical Health [GPH] and Global Mental Health [GMH]), and work productivity and activity impairment (WPAI:SHP). Of 271 participants, 76.4% experienced ≥1 AE (median 3 [range 014]), with the most common being fatigue (53.9%), pain (44.3%), and gastrointestinal symptoms (36.9%). Mean (SD) GPH and GMH T-scores were worse than general population averages (50) at 42.6 (7.0) and 44.4 (7.7), respectively. Mean (SD) activity impairment was 37.3% (24.6). Chronic AEs were associated with worse GPH/GMH T-scores and activity impairment ( < 0.05). The findings demonstrate the relationship between TKI-related AEs and QoL for US patients and the need for improved management strategies.

Existential distress and demoralization are common among patients with advanced cancer and are associated with impaired psychological well-being, reduced quality of life and difficulties in end-of-life adjustment. Meaning-Centered Psychotherapy (MCP), grounded in Viktor Frankl's logotherapy, was developed to address these existential dimensions of suffering. This narrative review synthesizes evidence from randomized and controlled studies evaluating MCP in adults with advanced cancer and discusses its clinical relevance within supportive and palliative care. Across studies, MCP demonstrated consistent improvements in meaning in life and spiritual well-being, with more modest effects on depressive symptoms and variable effects on anxiety and global quality of life. The available evidence supports MCP as a feasible and clinically relevant intervention for addressing existential distress, demoralization and loss of meaning in advanced cancer. Future research should examine long-term outcomes and implementation within routine oncology care.

BACKGROUND: Patients with hematologic malignancies frequently face complex, repeated treatment decisions that may increase decision fatigue (DF) risk. However, evidence on DF and its correlates in this population remains scarce. This study aimed to investigate the level of DF and identify associated factors among patients with hematologic malignancies. METHODS: A cross-sectional study was conducted with 322 patients receiving treatment at a tertiary hospital in Anhui, China, between October 2024 and May 2025. Participants completed validated scales assessing DF, decision preparation, decision self-efficacy, anxiety, depression, and sleep quality. Independent-samples t-tests, one-way analysis of variance (ANOVA), Pearson correlation analysis, and multiple linear regression were performed to identify factors associated with DF. RESULTS: The mean DF score was 13.30 ± 5.02, which was close to the midpoint of the 0-27 Decision Fatigue Scale. DF was negatively correlated with decision preparation and decision self-efficacy (both < 0.001), and positively correlated with anxiety, depression, and poor sleep quality (all < 0.001). Female gender, caregiver presence, shorter disease duration, disease recurrence, lower decision preparation, lower decision self-efficacy, and poorer sleep quality were independently associated with higher DF levels (all < 0.05). The regression model explained 69.0% of the variance in DF. CONCLUSION: Patients with hematologic malignancies exhibit decision fatigue levels near the scale midpoint, which are associated with multiple psychological and contextual factors. These findings can inform the development of patient-centered decision support strategies, though longitudinal and interventional studies are needed to confirm causal pathways and intervention efficacy.

BACKGROUND: Myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) is a rare demyelinating disorder with evolving diagnostic and treatment landscape. Real-world evidence on treatment patterns, access, and disease burden remains limited, particularly in China. OBJECTIVES: To characterize the patient journey, treatment patterns, healthcare resource utilization (HCRU) and multidimensional disease burden of MOGAD in China. DESIGN: Nationwide, cross-sectional electronic survey. METHODS: Patients with MOGAD and their caregivers completed an electronic survey capturing diagnostic and treatment history, HCRU, and patient-reported outcomes. Data were stratified by age and treatment phases. Multivariable linear regression was used to identify determinants of health-related quality of life (HRQoL). RESULTS: The cohort (n=336) was predominantly pediatric (69.6%). Corticosteroids remained the most widely used across treatment phases. The use of steroid-sparing immunosuppressants increased during maintenance treatment and showed age-specific patterns (SMD=0.9): children used intravenous immunoglobulin more often (57.7%), whereas adults more frequently received mycophenolate mofetil (54.2%). Barriers to treatment access were reflected by distance to obtain care and profound economic burden with high out-of-pocket expenses (up to 100% of total expenditure), while 66.7% of participants reported lack of reimbursement as a major obstacle. Despite largely preserved physical function, HRQoL remained reduced (SF-6Dv2 0.66) with high productivity loss mainly driven by presenteeism. Withdrawal from education/employment was the strongest predictor of reduced HRQoL (β = -0.252, p<0.001), exceeding clinical and treatment-related factors. Caregiver burden was considerable, with 43% requiring leave from work/school, and their high levels of psychosocial distress were evidenced by anxiety and depression screening scores. CONCLUSIONS: Real-world management of MOGAD in China is characterized by persistent use of corticosteroids and barriers of access to steroid-sparing immunotherapies. These constraints are associated with impaired quality of life and substantial socioeconomic burden. Improving access to effective and affordable maintenance therapies and strengthening multidisciplinary support may improve long-term outcomes for patients and caregivers.

BACKGROUND: Sex differences in the prevalence and presentation of depression and anxiety are well-established, yet disparities in the underlying network structure and potential causal relationships between symptoms, particularly under significant stress, remain less understood. Understanding these network differences is crucial for elucidating mechanisms and tailoring interventions. This study explored sex differences in the network structure of depression, anxiety, and co-occurring symptoms (posttraumatic stress disorder [PTSD] symptoms, insomnia, and fear reactions) in an adult population. METHODS: A cross-sectional survey was conducted among adults ( = 1,191, 684 women, aged 18-40) in Shanghai during a period of significant acute public health stress (pandemic citywide lockdown). Participants reported symptoms of depression (Patient Health Questionnaire [PHQ]), anxiety (Generalized Anxiety Disorder [GAD]), PTSD (intrusion, avoidance), insomnia (Insomnia Severity Index [ISI]), and fear reactions. Partial correlation networks examined overall symptom connectivity. Bayesian network (BN) analysis generated directed acyclic graphs (DAGs) to infer potential directional dependencies. Analyses were conducted by sex. RESULTS: Distinct sex-specific symptom network patterns emerged. Anxiety and intrusion symptoms were most central for women, while depression was most central for men. Overall network connectivity was significantly higher in women. Critically, BN analysis identified a more complex architecture of probabilistic dependencies in women, evidenced by a greater number of directed edges compared to men. The men's DAG indicated a relatively sparse structure with fewer directional pathways between symptoms. CONCLUSIONS: Men and women exhibited distinct distress symptom network structures under acute stress. Specifically, anxiety and intrusion emerged as central nodes in women, indicating that they may represent promising intervention targets to prevent symptom escalation, while depressive symptoms were more central to men. These findings highlight the importance of sex-sensitive psychological first aid during public health crises and establish an empirical foundation for the development of sex-informed, process-oriented interventions in future research.

BACKGROUND: Significant racial inequities exist in perinatal mood disorders and diagnoses. Traditional postpartum care consists of a singular six-week visit, which leaves many individuals feeling unsupported. Postpartum home visiting programs have demonstrated effectiveness in reducing symptoms of perinatal depression. Preliminary evidence suggests that cash transfers can improve both mental health and maternal health. METHODS: This study uses the Birth Justice Collaborative Postpartum Support Pilot to evaluate how home visiting coupled with cash transfers supports maternal mental health. Two focus groups (Black, = 3, American Indian, = 3) with home visitors (HVs) were conducted in January 2025. Authors used a semi-structured guide focused on gleaning insights from the HVs' perspective. Then inductive coding and thematic analysis were used to elucidate learnings. RESULTS: Six themes were illuminated regarding the role of the HV and how they supported postpartum families. Overall HVs spoke highly of this pilot and deemed it successful. HVs reiterated that this program is necessary. The most notable limitations of the pilot were addressing the sustainability of the home visiting workforce and the lack of cultural alignment in the Family Spirit curriculum with Black participants. DISCUSSION: HV and cash transfers support perinatal mental health through a variety of ways. Insights from HVs reveal this care is needed and is well received, but it requires flexibility to tailor support and attentive leadership to facilitate the conditions for HVs to thrive. A well-supported perinatal workforce can, in turn, provide adequate care, leading to improved mental health for postpartum families.

OBJECTIVES: Adolescent obesity is associated with increased rates of depression and suicidality. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are increasingly used to treat pediatric obesity, yet concerns remain regarding potential psychiatric effects. This study evaluated changes in depressive symptoms and suicidality screening scores among adolescents with obesity treated with GLP-1RAs in a pediatric endocrinology setting. We evaluated changes in depressive symptoms and suicidality following initiation of GLP-1RA therapy in adolescents with obesity. METHODS: We performed a retrospective chart review of adolescents aged 12-21 years with obesity treated with liraglutide or semaglutide at a single academic center between June 2022 and December 2024. Demographic, clinical, and psychosocial data were extracted from the electronic health record at baseline and follow-up. Depressive symptoms or suicidality were screened at clinic visits per protocol using either the Patient Health Questionnaire-9 (PHQ-9) or the Ask Suicide-Screening Questions (ASQ), respectively. Analyses were restricted to patients with paired baseline and follow-up assessments using the same instrument. Paired nonparametric tests were used for longitudinal comparisons. RESULTS: Forty-four adolescents met inclusion criteria. Among patients with paired PHQ-9 data (n=15), the median PHQ-9 score decreased significantly from 6 (IQR 2-14) at baseline to 1 (IQR 0-5) at follow-up (p=0.003), independent of changes in BMI. Among patients with paired ASQ data (n=23), no increase in suicidality or new suicidal ideation was observed. CONCLUSIONS: In this small, exploratory retrospective review, no evidence of short-term psychological harm or increased suicidality was observed among adolescents receiving GLP-1RA therapy. These findings support the short-term psychosocial safety of GLP-1RA therapy in adolescents with obesity. Larger prospective case-control studies are needed to better characterize psychiatric safety and psychosocial outcomes.

BACKGROUND: Severe COVID-19 frequently required prolonged intensive care, including mechanical ventilation or extracorporeal membrane oxygenation (ECMO). Survivors of such critical illness may develop post-traumatic stress disorder (PTSD). METHODS: We conducted a single-center retrospective follow-up study of COVID-19 ICU survivors at Saarland University Medical Center, Germany, assessing ICD-11 trauma-related disorders using the validated International Trauma Questionnaire (ITQ) and analyzing associations with clinical factors. RESULTS: Of 110 eligible patients, 42 (38.2%) valid datasets were obtained. The overall prevalence of ICD-11 trauma-related disorders (PTSD or CPTSD) was 23.8% (95% CI 12.1-39.5%; n = 10), with PTSD diagnosed in 6 participants (14.3%; 95% CI 5.4-28.5%) and CPTSD in 4 participants (9.5%; 95% CI 2.7-22.6%). No statistically significant associations were found for any of the examined variables. Exploratory subgroup analyses revealed numerically higher rates of trauma-related disorders in patients with prior psychiatric treatment (40.0% vs. 21.6%), ECMO therapy (33.3% vs. 16.7%), or renal replacement therapy (50.0% vs. 17.6%); however, these findings should be interpreted with caution given the limited sample size. CONCLUSIONS: Nearly one quarter of COVID-19 ICU survivors met the diagnostic criteria for PTSD or CPTSD, a prevalence comparable to that observed in other critically ill populations. No statistically significant associations were identified, and the observed subgroup differences should be regarded as exploratory and hypothesis-generating. The reported prevalence of PTSD/CPTSD highlights the potential value of systematic screening for trauma-related disorder and the integration of psychological support into post-ICU care. Larger prospective multicenter studies are needed to confirm these findings and further characterize potential risk factors. TRIAL REGISTRATION: The study was reviewed and approved by the Ethics committee of the Medical Association of Saarland (Number 98/22).

BACKGROUND: The number of adults in need of psychiatric care is increasing in Sweden. To meet this need, new working methods are implemented. Home-based mobile specialist psychiatric nursing teams (SPOT) are being introduced to function as a complement to outpatient care and inpatient care, but still little is known about how healthcare professionals experience such efforts. The purpose of this study was thus to capture mental healthcare professionals' experiences of the early phase of the introduction of SPOT. METHODS: Focus group discussions and semi-structured interviews were conducted with 11 mental healthcare professionals, including nurses, psychiatric aides working within psychiatric care and on the SPOT team and psychiatrists who had a consultative role in SPOT. The data was inductively analysed through reflexive thematic analysis. RESULTS: The discussions and interviews revolved around three themes: The phases and conditions of the change, Opportunities and challenges in the new form of intermediate care and Care in the patient's home for patient empowerment and engagement. Different perspectives on the new form of care emerged and many were positive about patients' increased engagement in care when it was offered in the home environment. However, it was also emphasised that the need for different forms of care remains and that a new level of care should not exclude other forms of care. The results further showed a need to engage and offer continuous support to healthcare professionals at different levels when new working methods are introduced. Specifically, support from managers and increased competence and skills development in performing new work tasks were requested. CONCLUSIONS: Providing care in the home environment through SPOT interventions can help increase patients' engagement in their own care. Preparing and equipping healthcare professionals at all levels and offering them knowledge support and influence in the introduction of new forms of care is important to reduce the vulnerability that professionals may initially experience in change processes and new ways of working.

Early detection and intervention are important components of contemporary psychiatric care. They aim to identify emerging mental disorders and clinically relevant at-risk states early on so as to provide timely, needs-based support. This article discusses the rationale, structure, and clinical experience of a specialized outpatient service for early detection and intervention at the Medical University of Vienna and presents an analysis of service uptake/patient characteristics. Located within a tertiary psychiatric university hospital, the service offers low-threshold access, structured diagnostic assessments, multidisciplinary care, and longitudinal monitoring. Patient characteristics are presented based on a retrospective descriptive analysis of routine clinical data collected since 2014, illustrating the heterogeneity of help-seeking individuals presenting with at-risk states, including diverse diagnostic profiles and functional needs. Our findings underscore the importance of individualized, stage-specific care that goes beyond transition prediction to focus on current distress, psychosocial functioning, quality of life, and reducing symptom burden. Integrated early detection services may improve access to care, ensure continuity of treatment, and enable timely intervention for individuals at risk for or in the early stages of psychosis.

PURPOSE: Returning to work and maintaining an adequate ability to work serve as key indicators of quality of life, psychological well-being and psychosocial adjustment. Therefore, this study aims to analyze the impact of breast cancer treatments on return to work (RTW), work ability (WA), and sick leave (SL) among breast cancer survivors. METHODS: A systematic review was conducted according to the PRISMA guidelines. The sample consisted of 26 studies published between 2016 and 2025, including prospective multicenter cohorts and national registries from fifteen countries across four continents, with more than 25,000 participants. A methodological quality assessment and a narrative synthesis were performed to synthesize the results. RESULTS: Chemotherapy is the most consistent predictor of prolonged SL, delayed RTW, and significantly reduced WA. Radical surgery and axillary lymph node dissection (ALND) are associated with a significantly delayed RTW due to physical sequelae. While outcomes showed strong relationship with clinical factors, certain psychosocial variables such as depression, anxiety, and low self-efficacy seemed to act as important secondary factors that can further complicate the process. CONCLUSION: The findings suggest that more invasive or aggressive treatments (chemotherapy, ALND, and radical surgery) were associated with poorer outcomes on RTW, WA, and SL. Furthermore, the clinical recovery associated with treatment completion did not necessarily equate to a functional recovery in WA that facilitated a successful RTW. Thus, it is necessary to explore in depth the impact of cancer treatments on WA, alongside psychosocial variables, to design multidisciplinary interventions that enable sustainable occupational reintegration. REGISTRATION: PROSPERO 2026 (CRD420261322638).

To design network-based treatments, it is critical to understand dynamic changes in brain networks over time. We comprehensively examined network structure using regional activation-only, pairwise-coactivation-only, and systems-level maximum entropy models (MEM) applied to the Human Connectome Project-Early Psychosis (HCP-EP) resting fMRI data (patients = 109, controls = 56). The MEM integrates regional activation levels and pairwise correlation-based functional connectivity (FC), providing the potential for better characterization of clinically meaningful brain states and how they change over time. Using the HCP/Glasser atlas to define brain regions within the default mode (DMN) and dorsal attention (DAN) networks, group differences in regional activation, graph measures of FC, and MEM features such as transition rates between minima in an energy landscape along with correlations with cognitive and psychopathological measures were examined. Psychosis was associated with reduced activation in several regions and multiple FC graph metric alterations. MEM demonstrated a wider variety of DMN and DAN activation/deactivation configurations, with more frequent switching between them, more pronounced network configuration differences and higher basin transition rates with reduced basin dwell times suggesting temporally unstable network configurations, meaning the brain cannot rely on any particular configuration for cognitive processing. Activation of only three regions correlated with working memory, but none of the FC metrics did. MEM features, in particular basin transitions and total energy, correlated negatively with working memory. Our findings suggest that MEM provides unique information, specifically attenuated inter-network connectivity with reduced stability of DMN and DAN brain states, to characterize networks as targets and their features as markers for novel treatment development.

Autistic individuals show elevated rates of co-occurring neurodevelopmental and mental health conditions, yet the genetic architecture of those comorbidities remains unclear. Using phenotypic (N = 74,204) and genetic (N = 17,582) data from the SPARK study, we investigated the factor structure, heritability, genetic correlation with autism (pleiotropy) and corresponding conditions in the general population (additivity). First, confirmatory factor analysis identified three correlated factors mirroring general population patterns: behavioural (ADHD, disruptive behaviour disorders), cothymic (depression, anxiety), and thought disorder (schizophrenia, bipolar). Second, all three factors had significant SNP heritabilities whilst rare variants were not associated with the tested factors in our sample. Third, polygenic scores and genetic correlations revealed positive shared genetics between the three factors and corresponding conditions in the general population but not with autism, supporting the additivity hypothesis. Fourth, within-family analyses (N = 5236 trios) demonstrated direct but not indirect genetic effects for the behavioural and cothymic factors. In sum, we find evidence for additive effects of other genetic factors in contributing to some latent co-occurring neurodevelopmental and mental health conditions in autism.

Adolescence represents a critical neurobiological period marked by a developmental "mismatch" between early-maturing limbic systems and the later-maturing prefrontal cortex, conferring heightened vulnerability to the onset of psychiatric disorders. This review synthesizes global epidemiological trends, differentiates true increases in morbidity from diagnostic inflation, and integrates evidence-based intervention strategies. In high-income countries, youth depression, suicide mortality, and self-harm have risen substantially, supported by objective indicators of illness severity that extend beyond changes in diagnostic practices. Key environmental drivers include pervasive digital engagement, cyberbullying, sleep disruption, and academic pressure, with sleep disturbances emerging as a central transdiagnostic risk factor. The COVID-19 pandemic accelerated these pre-existing trajectories of mental health deterioration, with particularly marked effects on eating-disorder incidence and social-emotional development. To address these challenges, we suggest a three-tiered intervention framework. Universal approaches should emphasize regulation of digital environments, implementation of Social-Emotional Learning, and institutional support for regular physical activity. Selective interventions should target high-risk youth by proactively monitoring sleep health and mitigating achievement-related stress in academically competitive settings. Indicated care requires integrated delivery of evidence-based psychotherapies alongside structured return-to-learn protocols following psychiatric hospitalization. Ultimately, translating epidemiological risk into effective prevention demands a shift from reactive, diagnosis-centered models to proactive frameworks that prioritize early risk reduction and the reinforcement of protective factors. By fostering environments that promote circadian stability, physical activity, emotional regulation, and peer connectedness, youth mental health can be strengthened as a foundation for societal well-being, resilience, and adaptive functioning in an increasingly complex world.

Co-production is increasingly recognised as central to improving the quality, relevance and ethical integrity of mental health science, yet evidence is still needed on how lived experience involvement can be meaningfully embedded and sustained in complex research settings. Global Alliance for Living Evidence on Anxiety, Depression and Psychosis (GALENOS) is a Wellcome-funded collaboration conducting living systematic reviews and evidence triangulation, with people with lived experience contributing as Experiential Advisors and through a Global Lived Experience Advisory Board. This perspective uses GALENOS as a case example to reflect on what meaningful co-production practically requires especially in the context of large-scale, technical and international collaborations. It draws on a collective reflection designed and led by people with lived experience, developed through workshops and written contributions involving lived experience contributors, researchers and project-support staff. Discussions were organised around lived experience involvement, capacity development, diversity and representation and influence in strategic decision-making. Across these areas, contributors identified that experiential knowledge needs to become consequential, participation must be supported through care and flexibility, diversity must shape interpretation rather than representation alone and influence must be embedded in governance and decision-making. GALENOS shows that co-production is not a fixed method but an evolving relational practice requiring practical infrastructures for accessibility, accountability, continuity and ethical care.

BACKGROUND: Conflicting evidence from observational studies and randomised trials has created uncertainty about the association between attention-deficit/hyperactivity disorder (ADHD) medication use and self-harm. OBJECTIVE: To assess the risk of incident self-harm associated with use of ADHD medication across multiple healthcare systems. METHODS: We conducted a multinational self-controlled case series study using a common data modelling approach to assess the risk of self-harm among individuals treated with ADHD medication across population-based databases from Hong Kong, New Zealand, South Korea, Taiwan and the United Kingdom. We included individuals who initiated ADHD medication and had a record of self-harm between 2001-2020. Incidence rate ratios (IRRs) for self-harm were calculated using conditional Poisson regression, comparing three risk periods of ADHD medication exposure (ie, the 90 days before medication initiation, the first 90 days of medication use and the subsequent treatment period) to non-exposure periods. Adjusted IRRs and 95% CIs were estimated for various risk periods. Estimates from each site were pooled using a random-effects model. FINDINGS: A total of 461 024 individuals with at least one prescription for ADHD medication were included, of whom 6847 had an incident self-harm event during the observation period. The risk was highest during the 90 days before medication initiation (pooled adjusted IRR: 2.58; 95% CI 2.12 to 3.13), followed by the first 90 days of medication use (pooled adjusted IRR: 1.78; 95% CI 1.23 to 2.57), and lowest in the subsequent treatment period (pooled adjusted IRR: 1.27; 95% CI 1.01 to 1.60). Results were consistent across included databases. CONCLUSIONS: While the use of ADHD medication was associated with self-harm, the highest risk occurred during the unexposed period immediately before starting treatment. The consistent findings across various health systems do not support ADHD medications as the main driver of self-harm. Instead, the increased risk observed prior to treatment may be related to untreated ADHD features. CLINICAL IMPLICATIONS: Although our findings provide reassurance that ADHD medications do not appear to be the main driver of the increased self-harm risk, the persistently elevated risk highlights the need for ongoing clinical monitoring and counselling before and during treatment.

INTRODUCTION: During pregnancy, physiological and psychological factors influence eating behaviour and food preferences. Food cravings are common in pregnancy and contribute to excessive gestational weight gain (GWG). Excessive GWG is present across all body mass index (BMI) categories and is associated with adverse outcomes. Outside of pregnancy, highly palatable food cues activate brain regions involved in reward and attention, which may influence eating behaviour and behavioural responses. However, brain and behavioural responses to food cues across pregnancy, and their association with psychological and metabolic factors, remain poorly understood. This study aims to investigate spatiotemporal brain responses to visual food cues across individuals with different BMI categories and their associations with behavioural, psychological and metabolic outcomes during pregnancy. METHODS AND ANALYSIS: This is a prospective observational cohort study conducted at the Lausanne University Hospital, Switzerland. 94 pregnant individuals (47 healthy normal weight and 47 with overweight/obesity) will be assessed at 12-16 and 31-36 weeks of gestational age from November 2024 to September 2026. Data collected for the primary outcomes include electroencephalography-based brain responses to validated visual food cues varying in fat and carbohydrate content, behavioural responses to the same cues using a gamified smartphone Go/NoGo task. Secondary validated outcomes include heart rate variability (Actiheart), body composition (InBody S10), glycated haemoglobin (Afinion), cardiorespiratory fitness (The Chester step test), snack intake, eating behaviour (Intuitive Eating Scale-2, Three-Factor Eating Questionnaire-Revised), food cravings (Food Craving Questionnaire-state), mood and depressive symptoms (Edinburgh Postnatal Depression Scale). Statistical analyses include group comparisons, longitudinal analyses and regression models adjusted for potential sociodemographic/medical confounders. ETHICS AND DISSEMINATION: All participants will provide written informed consent. The Human Research Ethics Committee of the Canton de Vaud approved the study protocol (CER-VD 2023-01462). Findings will be disseminated through peer-reviewed publications, (inter)national conferences and shared with healthcare professionals and stakeholders to inform strategies for improving maternal health.

BACKGROUND: Insomnia disorder is a highly prevalent and impactful condition, especially among veterans. Cognitive Behavioral Therapy for Insomnia (CBTi) is the standard of care for insomnia disorder, but access is limited. Self-directed digital interventions, such as digital CBTi (dCBTi), may mitigate barriers to access. Although dCBTi reduces insomnia severity and mental health symptoms, most patients do not fully engage in self-directed digital interventions, including dCBTi, without support. METHODS: Participants are veterans referred from healthcare providers to a digital CBTi clinical service across five VA sites. In this multi-site pragmatic Hybrid Type 2 implementation-effectiveness trial, referred patients were assessed for contraindications to dCBTi and randomized to one of two levels of adjunctive support for dCBTi. Effectiveness outcomes include insomnia severity, subjectively assessed sleep, and mental health symptoms. Trial outcomes are organized according to the RE-AIM framework. Reach and adoption are evaluated at the patient and provider/staff levels, respectively. Implementation is formatively evaluated through patient and provider semi-structured interviews. CONCLUSION: Since the prevalence of insomnia disorder among veterans far outweighs VA's capacity to deliver gold-standard treatment through any single modality, an array of treatment options is needed. If Coached dCBTi is found to increase engagement, clinical outcomes are likely to improve when implemented in VA facilities. The design of this trial should inform the best approach to implementing dCBTi into clinical care and the extent to which telephone coaching enhances treatment engagement and clinical outcomes. CLINICAL TRIALS: Gov Identifier: NCT05558475.

The bidirectional interaction between the gut microbiota and the CNS, referred to as the microbiota-gut-brain axis, has gained recognition as a key regulator of stress responses and neuropsychiatric health. This review synthesizes evidence from preclinical and human studies conducted between 2010 and 2026, setting itself apart from previous reviews by focusing on the bidirectional connection between stress exposure and alterations in gut microbiota. It places particular emphasis on the molecular mechanisms involved, such as neuroinflammation, regulation of the HPA axis, neurotransmitter signaling, and how the microbiota contributes to stress adaptation. Growing evidence from preclinical and clinical research suggests that stress-induced disturbances in gut microbial composition can trigger systemic and neuroinflammation. This occurs through mechanisms such as increased intestinal permeability, translocation of lipopolysaccharides, and activation of TLR4 and NF-κB signaling pathways. Consequently, these immune disruptions adversely affect neurotrophic and neurotransmitter systems such as brain-derived neurotrophic factor (BDNF), serotonin, dopamine, and GABA contributing to anxiety, depression, cognitive impairments, and neurodegenerative conditions. Instead, deliberate modulation of the gut microbiota through probiotics, psychobiotics, fermented foods, and dietary strategies has shown potential to restore microbial balance. Such interventions can help reduce overactivation of the hypothalamic-pituitary-adrenal (HPA) axis, reduce levels of IL-6 and TNF-α, and promote BDNF-driven neuroplasticity. Experimental studies highlight how specific bacterial strains may influence outcomes under stress by enhancing CREB phosphorylation, maintaining tight junction integrity in the gut, and modulating microglial activation. Emerging therapeutic approaches such as fecal microbiota transplantation and postbiotic metabolites, including SCFAs, have also demonstrated promising potential for clinical translation.

BACKGROUND: The prevalence of substance use and mental health disorders is rising in pregnancy, however there is a paucity of evidence of how co-occurring diagnoses affect maternal and neonatal wellbeing. OBJECTIVE: To examine the association between co-occurring anxiety and/or depression and substance use in pregnancy and adverse perinatal outcomes. STUDY DESIGN: This is a retrospective cohort study analyzing linked vital statistics and hospital discharge data from all births in California between 2008 and 2020. Individuals with anxiety/depression and co-occurring substance use disorders were identified using International Classification of Disease (ICD-9-CM and ICD-10-CM) codes. Statistical analysis was performed using Chi-square tests and multivariable Poisson regression models. RESULTS: A total of 139,563 pregnant individuals with anxiety/depression met inclusion criteria, 12,235 (8.8%) had co-occurring substance use. Individuals with anxiety/depression and stimulant or polysubstance use had increased risk of adverse maternal outcomes compared to those with anxiety/depression alone. Individuals with anxiety/depression and stimulant use had the highest risk of hypertensive disorder (aRR=1.65, 99.5% CI 1.31, 2.07) and severe maternal morbidity (aRR=2.06, 99.5% CI 1.38, 3.09). Co-occurring anxiety/depression and substance use also negatively impacted neonatal outcomes. Anxiety/depression and opioid use was associated with an increased risk of preterm birth <37 weeks (aRR=1.76, 99.5% CI 1.40, 2.20), neonatal intensive care unit admission (aRR=3.65, 99.5% CI 3.23, 4.12), and respiratory distress syndrome (aRR=2.39, 99.5% CI 1.83, 3.12). The risk of having a small for gestational age neonate was increased for co-occurring diagnoses across all types of substance use with the exception of alcohol use. CONCLUSION: Substance use during pregnancy, especially stimulant or polysubstance use, in individuals with anxiety/depression compared to those with anxiety/depression alone was associated with worse maternal and neonatal outcomes that varied depending on the type of substance. These findings highlight areas to target counseling and intervention to mitigate perinatal morbidity.

BACKGROUND: Suicidal ideation (SI) is a leading risk factor for suicide death, with a lifetime prevalence of 35-40% in psychiatric populations. However, the neurobiology of SI remains poorly understood. Preliminary work suggests an association between SI and neurophysiological measures derived from transcranial magnetic stimulation combined with electroencephalography (TMS-EEG). METHODS: This study aims to test the association between SI and two TMS-EEG measures: the negative peak at 100ms (N100) and the area under the curve (AUC) of the global mean field amplitude (GMFA). In this multi-site data synthesis, cross-sectional TMS-EEG data from 299 adult participants with major depressive disorder and at least 1 ineffective antidepressant trial were aggregated across five academic medical centers. Single-pulse TMS was delivered to the left dorsolateral prefrontal cortex (DLPFC) with simultaneous EEG recording. RESULTS: The N100 peak amplitude between 80 to 130ms, as well as the AUC-GMFA between 55 to 275ms, were extracted for each participant. Ordinal regression analysis revealed a significant positive association between more negative N100 peak amplitude in the left DLPFC and greater severity of SI (OR=1.52, p=0.002, 95%CI [1.17;1.98]), independent of age, sex, depression severity, and study site. There was no significant association between GMFA and SI. CONCLUSION: N100 peak amplitude in the left DLPFC is a neurophysiological correlate of SI which may reflect a neurophysiological link between GABAergic inhibitory dysregulation and the pathophysiology of SI. Further research is needed to validate the findings using sham TMS-EEG and subsequently test the utility of N100 in the left DLPFC as a biomarker of SI and a possible treatment target.

BACKGROUND: Following the full-scale Russian invasion of Ukraine, scalable psychological interventions that can be delivered flexibly are urgently needed, yet evidence on implementing group psychotherapy remains limited. This pilot study evaluated the feasibility, acceptability, and preliminary clinical outcomes of a culturally adapted, modular Empowerment group therapy delivered in face-to-face and online formats. METHODS: We conducted a single-arm feasibility pilot with N = 56 Ukrainian adult outpatients recruited into five groups (3 face-to-face; 2 online). Feasibility was assessed via retention rate, dropout and protocol adherence using predefined progression criteria. Acceptability was assessed using the CSQ-4 and qualitative feedback. Secondary outcomes included depressive symptoms, anxiety, and stress (PHQ-9, DASS-21), symptoms of post-traumatic stress disorder (PTSD) (PCL-5), somatic symptoms (SSS-8), quality of life (SF-36), and resilience (BRS). RESULTS: Feasibility outcomes met "go" progression criteria with a retention rate of 96.4%, a dropout rate of 3.6% and protocol adherence of 93%. Acceptability was high (CSQ-4 total M = 12.07, SD = 1.04). Secondary outcomes showed large and sustained improvements. The largest effects were observed for depressive symptoms (PHQ-9: d = 1.44), mental health-related quality of life (SF-36 Mental Health; d = 1.28), DASS-21 depression (d = 1.25), PTSD symptoms (PCL-5: d = 1.18), and somatic symptom burden (SSS-8: d = 1.16). Improvements were generally larger in face-to-face groups. CONCLUSIONS: This pilot shows the implementation of Empowerment group therapy is feasible in Ukrainian outpatients during an ongoing war. Preliminary clinical outcomes show substantial improvements across multiple symptom domains and quality of life. Findings support progression to a randomized controlled trial to evaluate effectiveness, durability of outcomes, and cost-efficiency, and to clarify optimal delivery conditions for in-person versus online formats.

Resilience has become an integral component of theory and research in brain aging. Recent frameworks have provided guidelines for identifying and investigating resilience in the context of diversity (e.g., sex and risk exposure differences). We leverage a multi-factorial longitudinal approach to operationalize and predict pathways of resilience, stability and vulnerability as a function of differential within-person trajectory patterns of hippocampal volume and cognitive change. Participants included cognitively unimpaired (at baseline) older adults (n = 415; M age = 74.9; 59.9% Female) from the Alzheimer's Disease Neuroimaging Initiative with longitudinal imaging and cognition data, plus multimodal risk indicators. We used latent class growth analyses to identify hippocampal and cognitive trajectory classes. Machine learning applications identified risk indicators associated separately by pathway in the entire sample and disaggregated by sex. Based on differential combined class membership, we identified three subgroups: resilience (declining hippocampal/stable cognitive trajectories), stable (stable hippocampal/stable cognitive trajectories), vulnerable (stable hippocampal/declining cognitive trajectories). Leading risk indicators of resilience (e.g., lower plasma Aβ1-42) and vulnerability (e.g., lower education) originated from the biological and demographic domains. Leading risk indicators of stability originated from the biological and genetic domains (e.g., higher CSF Aβ1-42, lower polygenic hazard score). Sex-disaggregated results highlighted indicators unique to the females, such as higher body mass index (stability) and lower geriatric depression score (stability, vulnerability). Pathway patterns of resilience, stability and vulnerability were characterized objectively in initially cognitively unimpaired older adults based on specified hippocampal and cognitive trajectory combinations. Risk factors from a broad range of modalities should be considered in future research.